血清人附睾蛋白4联合外泌体miRNA-200a/200b/200c用于糖链抗原125阴性卵巢上皮癌早期诊断的价值

doi:10.3969/j.issn.1006-5725.2023.19.022

Abstract

Abstract:

Objective To investigate the value of serum human epididymal protein 4 （HE4） combined with micrornas （mirnas） -200a/200b/200c in exosomes in the early diagnosis of glycochain antigen 125 （CA125） negative epithelial ovarian carcinoma （EOC）. Methods A total of 120 patients with CA125-negative EOC were selected as the study group， and 115 patients with ovarian epithelial benign tumor admitted during the same period were selected as the benign group. Another group of 107 healthy women who underwent physical examination in wuhan firsthospital were selected as the control group. The levels of HE4， CA125， miRNA-200a， miRNA-200b and miRNA-200c were compared among the three groups. The value of serum indexes in differentiating CA125-negative EOCs and benign ovarian epithelial tumors was analyzed by receiver operating characteristic （ROC） curve. Results The levels of HE4， miRNA-200a， miRNA-200b and miRNA-200c in the study group were significantly higher than those in the benign group and control group， statistically significant differences between the groups （P < 0.05）. ROC analysis confirmed that serum HE4， miRNA-200a， miRNA-200b， and miRNA-200c could be used for the diagnosis of CA125-negative EOC. The combined diagnosis by HE4+miRNA-200a/b/c could obtain a higher area under the curve than the single or pair-based diagnosis （P < 0.05）. Logistic stepwise regression analysis confirmed that， HE4 ≥ 163.110 pmol/L， miRNA-200a ≥ 2.700 2^-△CT， miRNA-200b ≥ 1.665 2^-△CT， miRNA-200c≥ 1.395 2^-△△CT were the risk factors for CA125-negative EOC （P < 0.05）. Conclusion Serum HE4， miRNA-200a， miRNA-200b and miRNA-200c can be used in the early diagnosis of CA125-negative EOC. The diagnosis with the four indicators combined has higher sensitivity and specificity.

Key words: ovarian epithelial carcinoma, cancer antigen 125, human epididymal protein 4, miRNA, miRNA-200a, miRNA-200b, miRNA-200c

CLC Number:

R737.31

Xiangbing JIANG,Lifei WANG,Chunlin WU,Feng LI,Donghua WANG,Xuemei. GAO. Values of serum HE4 combined with exosome miRNA-200a/200b/200c in the early diagnosis of CA125 negative ovarian epithelial carcinoma[J]. The Journal of Practical Medicine, 2023, 39(19): 2541-2545.

Figures/Tables 6

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References 23

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miRNA		引物序列	引物长度（bp）
miRNA-200a	正向	5′-GGCCCGTAACACTGTCTGGTAA-3′	72
miRNA-200a	反向	5′-CAGTGCAGGGTCCGAGGT-3′	72
miRNA-200b	正向	5′-CATTCCGGACTCGAGCACTTGTGT-3′	66
miRNA-200b	反向	5′-GCTACGTTGAGTCAACTAGTAACG-3′	66
miRNA-200c	正向	5′-TGGAGGCCAGTTCACTTCGA-3′	80
miRNA-200c	反向	5′-ATCTCCAGTGCAGCGGCCTCCTG-3′	80
U6	正向	5′-CTCGCTTCGGCAGCACA-3′	60
U6	反向	5′-AACGCTTCACGAATTTGCGT-3′	60

组别	例数	HE4（pmol/L）	miRNA-200a（2^-△△CT）	miRNA-200b（2^-△△CT）	miRNA-200c（2^-△△CT）
研究组	120	492.10 ± 155.99	4.02 ± 0.94	3.41 ± 1.18	2.60 ± 0.84
良性组	115	64.79 ± 18.40^a	1.48 ± 0.48^a	1.23 ± 0.28^a	1.15 ± 0.15^a
对照组	107	48.68 ± 17.46^a	1.39 ± 0.42^a	1.17 ± 0.20^a	1.10 ± 0.14^a
F值		853.794	587.506	360.346	324.048
P值		< 0.001	< 0.001	< 0.001	< 0.001

指标	曲线下面积	标准误	P值	95%CI	最佳截断值	敏感度	特异性
HE4	0.844	0.027	< 0.001	0.791～0.897	163.110 pmol/L	0.817	0.835
miRNA-200a	0.828	0.028	< 0.001	0.773～0.883	2.700 2^-△△CT	0.800	0.835
miRNA-200b	0.809	0.029	< 0.001	0.751～0.867	1.665 2^-△△CT	0.800	0.765
miRNA-200c	0.814	0.030	< 0.001	0.756～0.872	1.395 2^-△△CT	0.800	0.817
HE4+miRNA-200a	0.877	0.023	< 0.001	0.832～0.923	-	0.817	0.817
HE4+miRNA-200b	0.846	0.027	< 0.001	0.794～0.898	-	0.808	0.774
HE4+miRNA-200c	0.855	0.026	< 0.001	0.804～0.906	-	0.817	0.867
HE4+miRNA-200a/b/c	0.938	0.017	< 0.001	0.905～0.970	-	0.867	0.948

变量	量化赋值
变量	1	0
HE4	≥ 163.110 pmol/L	< 163.110 pmol/L
miRNA-200a	≥ 2.700 2^-△△CT	< 2.700 2^-△△CT
miRNA-200b	≥ 1.665 2^-△△CT	< 1.665 2^-△△CT
miRNA-200c	≥ 1.395 2^-△△CT	< 1.395 2^-△△CT
CA125阴性EOC	是	否

自变量	β	标准误	Wald	P值	OR	95% CI
HE4 ≥ 163.110 pmol/L	0.901	0.355	6.447	0.011	2.461	1.228～4.932
miRNA-200a ≥ 2.700 2^-△△CT	1.565	0.638	6.012	0.014	4.785	1.369～16.725
miRNA-200b ≥ 1.665 2^-△△CT	0.557	0.272	4.191	0.041	1.745	1.024～2.974
miRNA-200c ≥ 1.395 2^-△△CT	0.901	0.403	5.015	0.025	2.463	1.119～5.421

Values of serum HE4 combined with exosome miRNA-200a/200b/200c in the early diagnosis of CA125 negative ovarian epithelial carcinoma

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